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A: At the 2007 American College of Veterinary Internal Medicine Forum in Seattle, Dr. Gabriele A. Landolt gave a lecture titled "Up to New Tricks: Interspecies Transmission of Influenza." Here are some relevant points:

Recently, the need to understand influenza host range has taken on increased significance. Specifically, the re-emergence of highly pathogenic avian H5N1 influenza A viruses in poultry, cats and humans throughout large parts of Asia, Europe and North Africa have triggered fears of an impending influenza pandemic.

Yet these viruses' apparent inability to efficiently spread from person-to-person, a requirement for full-scale emergence and maintenance of a new pathogen in a population, is an important reason why these avian H5N1 viruses have not yet sparked a full-blown pandemic. It has long been recognized that barriers exist that limit direct transmission of influenza viruses among species.

Moreover, the prevalence of influenza virus interspecies transmission appears to be dependent on the animal species involved.

For example, horses often have been regarded as isolated hosts for influenza viruses, although recent events clearly indicate that the species barrier for viruses jumping to or from horses is not absolute.

Avian reservoirs

Historically, only a limited number of influenza virus subtypes have circulated widely in mammalian populations. For example, in humans, only viruses of H1, H2, H3, N1 and N2 subtypes have been associated with widespread infection. In horses, influenza infections have been restricted largely to viruses of H7N7 and H3N8 subtypes, and only H1, H3, N1 and N2 subtypes have consistently been isolated from pigs.

In contrast, viruses of all 16 HA and nine NA subtypes have been recovered from wild waterfowl and seabirds. In these birds, influenza viruses are highly host-adapted, as evidenced in the low evolutionary rate of the viral genome (evolutionary stasis). Infection typically results in subclinical disease.

As the viruses preferentially replicate in the duck's intestinal tract, they are shed in high concentration in the feces, thereby contaminating lakes and ponds visited by these animals. As such, aquatic birds, particularly migrating waterfowl, represent a global reservoir of all subtypes of influenza viruses in nature from which novel viruses can emerge to infect mammalian species.

Indeed, viruses of avian origin have been the source of outbreaks of influenza in animals, such as seals, whales, mink, pigs and horses. The importance of the avian reservoir is further highlighted by the fact that the virus that caused the 1918 Spanish influenza pandemic, undoubtedly the most devastating pandemic known to man, derived all of its genes from an avian virus. Moreover, the pandemic strains of the 1957 Asian pandemic, as well as the 1968 Hong Kong pandemic, arose from genetic reassortment of contemporary human and avian influenza viruses.

Lastly, phylogenetic analyses demonstrate that viruses from aquatic birds were the ancestral precursors of all contemporary influenza viruses present in other species.

Evidence supports that barriers exist, limiting the direct transmission of influenza viruses from birds to mammals. For example, despite the fairly high prevalence of H5N1 viruses in birds in parts of Asia, transmission of the virus to humans remains sporadic. In addition, these viruses still do not appear to have developed the ability to transmit efficiently from person-to-person — a feature considered the chief prerequisite for pandemic emergence of influenza. Given this limited capacity for transmission and spread of avian viruses in humans, it is hypothesized that the emergence of an avian virus with pandemic potential requires prior adaptation of the virus in an intermediate host.

Role of intermediate host

As avian viruses of virtually all HA subtypes were able to infect and replicate in pigs, it has been postulated that these animals are logical intermediate hosts. As pigs are susceptible to infection with human lineage viruses, pigs may serve as mixing-vessel hosts for genetic reassortment between human and avian viruses. In fact, there are several well-documented examples of direct avian-to-pig transmission of influenza as well as instances where genetic reassortment of human and avian viruses was shown to have occurred in pigs.